Critically ill patients may die of Multiple Organ Dysfunction Syndrome (MODS) despite having their blood pressure, arterial oxygenation, and blood acid base status restored. Indirect evidence indicates that cellular hypoxia is the initial injury leading to death in these patients. This is a revised proposal to develop a noninvasive oximeter to measure skeletal muscle cellular oxygenation. Pulse oximetry revolutionized critical care by providing a noninvasive measurement of arterial hemoglobin oxygen saturation. The innovative goal of the present application is to go the next step and develop an instrument for noninvasively measuring skeletal muscle cellular oxygenation by determining intracellular myoglobin oxygen saturation. Preliminary data are presented that demonstrate the feasibility of the method. A research plan is proposed where a novel optical spectral analysis method, Multivariate Curve Resolution (MCR), is optimized to account for light scattering in tissue. The method will be validated by an independent measure of myoglobin saturation using Magnetic Resonance Spectroscopy (MRS). The utility of the instrument will be tested in a model of hemorrhagic shock in anesthetized rabbits. The ability to noninvasively monitor skeletal muscle cellular hypoxia has enormous potential for the treatment of critically ill patients. PUBLIC HEALTH RELEVANCE: This project will develop and test a new approach to assess cellular oxygenation in skeletal muscle. The approach analyzes spectral, or color changes from reflected light through the skin to determine how well oxygen is able to get into muscle cells, in an animal model of traumatic shock. This new approach may provide crucial new information that can be used for improving current therapies for people in shock, resulting from traumatic injuries.